Extracorporeal Membrane Oxygenators (ECMO) treat both newborns and adults in respiratory failure. Improved technology for longer-term ECMO use is desirable and would allow broader (children/adults/ cardiac support) and safer use. Present systems are based on either (1) microporous hydrophobic polypropylene hollow fibers (HF), which have adequate initial performance, but deteriorate over time due to fluid infiltration into pores which significantly reduces gas transport, or (2) non-porous silicone rubber membranes, which are more stable but have lower gas permeability, requiring larger priming volumes. In Phase I, we fabricated novel, high flux, perfluoronated coatings onto existing polypropylene HF for enhanced ECMO performance. Key accomplishments include: (1) successful conversion of commercial (Avecor and Terumo) microporous polypropylene HF membrane oxygenators (MO) systems into nonporous MO, (2) in vivo demonstration showing perfluoro-coated HF membranes with long-term stability of 24 hours, while the un-coated polypropylene control failed after only 12 hours, (3) in vitro tests showing minimal loss of O2 and CO2 transport into blood with perfluoro-coated HF. In Phase II, we will (A) optimize coating both internal HF lumen and external HF circumference of commercial polypropylene MO modules with our fluoronated coating and (B) demonstrate enhanced long-term MO stability via in vivo animal studies. PROPOSED COMMERCIAL APPLICATIONS Membrane oxygenators with high 02/CO2 transport and stable performance will enhance infant care plus allow broader use with children, adults (acute respiratory distress) and cardiac support. These non-porous membranes will also be key building blocks for intravascular oxygenators and oxygen delivery systems with enhanced blood side mass transport.